Osteoporosis is a growing problem worldwide, producing disability through development of fractures. Fracture pathogenesis is complex, involving both trauma to the skeleton and increased skeletal fragility. Low bone mass at the site of fracture is one of the principle determinants of skeletal fragility, and this is the principle focus of this program project, although other aspects of fragility are also being evaluated. Low bone mass among the elderly is related either to low peak bone mass, or increased rates of bone loss, and both aspects are being addressed. This application contains four projects and two cores. Johnson's project is related to the role of sex steroids and bone turnover in the acquisition of peak bone mass and bone loss. It also focuses upon the differences between black and white Americans, and the causes which may yield the black advantage in developing increased peak bone mass and lower fracture rates later in life. A sample of black and white males and females will be evaluated during the rapid period of growth in childhood and early adolescence to determine differences in rates of acquisition of bone, and what role bone turnover and hormonal concentrations may play. Similarly, a sample of black and white women and men over age 60 will be evaluated to, again, examine differences in rates of bone loss and associations with sex steroids (especially estrogen concentrations in males and females) and bone turnover. Christian's project extends our observations on the genetic contribution to the development of bone mass. It will search for genes associated with peak bone mass. 500 Caucasian and 250 African-American adult sibling pairs will be phenotyped. The genetic markers, highly informative microsatellites, will be performed by Sequana Therapeutics. Burr's project is focused on the relationship between bone turnover and the mechanical integrity of the skeleton. A dog study will use two bisphosphonates to reduce turnover and this will be related to histomorphometric changes and mechanical strength of the skeleton. Peacock's project will complete the trial of vitamin D and calcium undertaken in the previous application, and subsequently will study 350 black women and 150 black men, who will be compared to whites in variables related to bone strength, fall frequency, soft tissue distribution, and muscle strength. In addition, a case-control study will evaluate differences in black men, black women, and white men regarding hip fractures. Core A, the Epidemiology, Biostatistics, and Administrative Core, supports all projects in experimental design and analysis. Core B provides biochemical measures of hormones, markers of bone turnover, and calcium absorption for all four projects.